Improved system for inner ear drug delivery via trans-round window membrane injection

ABSTRACT

A system for the delivery of therapeutic substances to cavities of a patient. The system can include a handpiece tool coupled with a pump. The handpiece tool can include a shaft including a first portion of a channel coupled to a multi-input tubing. The handpiece tool can include an angled portion coupled with the shaft. The handpiece tool can include a second portion of the channel, wherein the angled portion positions a tip portion within a cavity, wherein the tip portion projects from the angled portion and includes an outlet and a third portion of the channel. The handpiece tool can include a collar a distance from the outlet, the collar configured to control a distance the tip portion projects. The handpiece tool can include a mixing chamber configured to receive the components of the drug and output the mixed drug via the third portion of the channel.

BACKGROUND OF THE DISCLOSURE

Delivery of therapeutics to the human inner ear can be challenging forclinicians. Two anatomic “windows” from the middle ear to the inner earexist, the oval and round windows. Each of these windows include asemi-permeable membrane. Drug delivery to the inner ear requires that atherapeutic substance cross one of these membranes.

SUMMARY OF THE DISCLOSURE

Inner ear drug delivery can use diffusion to cross one or both of themembranes of the anatomic windows to the inner ear. Relying on diffusionacross a membrane poses a number of difficulties. For example, diffusingtherapeutic substances across the membranes can introduce a lack ofprecision in terms of dose delivery. Relying on diffusion can also limitthe size and characteristics of therapeutic substance's moleculesbecause, for example, not all substances can diffuse across themembranes. Another example challenge is that the round window membranepermeability can vary between patients or during states of inflammation.The handpiece of the present disclosure can overcome these challenges bydelivering a therapeutic substance directly to the inner ear.

According to at least one aspect of the disclosure, a handpiece toolincludes a shaft that includes a first portion of a microfluidic channeland is configured to connect with a multi-input tubing to receive aplurality of fluids, such as from a pump. The handpiece tool can includean angled portion coupled with the tool shaft. The angled portion caninclude a second portion of the microfluidic channel. The angled portioncan be configured to position a tip portion of the handpiece within acavity of a patient. The tip portion can project from the angled portionand can include an outlet and a third portion of the microfluidicchannel. The handpiece can include a collar coupled with the tipportion. The collar can be a predetermined distance from the outlet. Thecollar can be configured to control a distance the tip portion projectsinto the cavity.

In some implementations, the handpiece tool can include a mixingchamber. The mixing chamber can include a mixing element to mix fluidsas the fluids flow along the length of the mixing chamber. The pump caninclude a second pump configured to flow a second fluid from a secondreservoir into the mixing chamber to mix with the first fluid in themixing chamber. The first pump can be a first pump type, and the secondpump can be a second pump type different than the first pump type. Thefirst pump can be configured to flow the first fluid and the secondfluid into the mixing chamber.

In some implementations, the first pump can be a lead screw-driven minisyringe pump, a 3-actuator pump, a mini peristaltic pump, or apneumatic/hydraulic-driven pump. In some implementations, the collar canbe configured to seat with a round window of a patient's cochlea.

According to at least one aspect of the disclosure, a method can includeestablishing a fluidic coupling between a handpiece tool and a pumpusing a tubing. The handpiece tool can include a microfluidic channelcoupled to the tubing to receive a plurality of fluids responsive tooperation of one or more pumps of the pump. The method can includeinserting a tip of the shaft of an angled portion of the handpiece toolinto a cavity of a patient. A collar coupled with the tip apredetermined distance from an outlet of the tip is configured tocontrol a distance the tip projects into the cavity of the patient. Themethod can include mixing, by a mixing chamber of the handpiece tool,the plurality of fluids received from the multi-input tubing to providea mixed fluid. The method can include outputting the mixed fluid via themicrofluidic channel through the outlet of the tip to within the cavityof the patient.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings are not intended to be drawn to scale. Likereference numbers and designations in the various drawings indicate likeelements. For purposes of clarity, not every component may be labeled inevery drawing. In the drawings:

FIG. 1 illustrates an example fluid delivery system.

FIG. 2 illustrates a block diagram of an example system for use in thesystem illustrated in FIG. 1.

FIG. 3 illustrates a side view of the example handpiece illustrated inFIG. 1.

FIG. 4 illustrates a cross-sectional view of the example handpieceillustrated in FIG. 1.

FIG. 5 illustrates a side view of the example handpiece illustrated inFIG. 1.

FIG. 6 illustrates an example tip portion for the handpiece illustratedin FIG. 1.

FIG. 7 illustrates an example handpiece with a compression fitting.

FIG. 8 illustrates an enlarged view of the tip of the example handpieceillustrated in FIG. 1.

FIGS. 9A and 9B illustrates the tip of the example handpiece insertedinto a round window.

FIG. 10 illustrates a block diagram of an example method to flow a fluidinto the cochlea with the system illustrated in FIG. 1.

DETAILED DESCRIPTION

The various concepts introduced above and discussed in greater detailbelow may be implemented in any of numerous ways as the describedconcepts are not limited to any particular manner of implementation.Examples of specific implementations and applications are providedprimarily for illustrative purposes.

The present disclosure discusses a handpiece tool for fluid delivery,such as in a drug delivery system. The system can include a handpieceand a pump (e.g., a micropump). The system can be used to deliverfluids, such as fluids that can include one or more drugs, to a cavitywithin the patient. For example, the handpiece can be inserted into themiddle ear via a surgical tympanotomy approach. The handpiece can enablea controlled injection of a therapeutic substance directly through theround window membrane and into the inner ear. The direct delivery of thetherapeutic substance to the inner ear can enable the delivery of aprecise amount of therapeutic substance into the inner ear. Because thetherapeutic substance is delivered directly to the inner ear, thedelivery of the therapeutic substance is not subject to limitations onmolecule size and inconsistent diffusion rates that are present whentherapeutic substances are diffused across the round window membrane.

FIG. 1 illustrates an example fluid delivery system 100. The system 100includes a handpiece 104 for the delivery of the drug to the bodycavity. The handpiece 104 is described in greater detail in relation toFIGS. 3-9, among others. The handpiece 104 can be coupled with a pump(e.g., pump 162 depicted in FIG. 2) via tubing 102. The tubing 102 canbe a fixed or static length, such as 15 centimeters, 12 inches, 1 meter,etc. The tubing 102 length can refer to a multi-input tubing fluidlycoupled to one or more pumps 162.

The system 100 is configured to deliver drug, therapeutic agents,fluids, or other materials to a human's natural cavities. The injectedsubstances can generally be referred to as fluids. The cavities caninclude, but are not limited to, the inner ear, ocular cavity, spinalcavity, oral cavity, anal cavity, urinary cavity, and/or cervix cavity.The system 100 can control the level of drug penetration, amount of drugdiffusion, volume of drug injected, and the flow rate of the injecteddrug.

FIG. 2 illustrates an block diagram of the system 100 in which a pump162 is provided to connect with the tubing 102 and handpiece 104 (e.g.,to cause the handpiece 104 to deliver drugs to the cavity of the body).The pump 162 can be a small, self-contained pump. The pump 162 can be awearable pump. The pump 162 can be self-contained by internallyincluding a power system to power the pump and one or more reservoirs tostore the fluid to be injected. The pump 162 can include a strap thatenables the pump 162 to mount or attach onto a surface. Mounting thepump 162 can increase stability of the pump 162. The pump 162 can be adistance (or proximity) from the handpiece 104, such as 10 centimeters(“cm”), 20 cm, or 30 cm from the handpiece 104. The proximity can referto the length of a tubing 102. The proximity of the pump 162 to thehandpiece 104 can limit the amount of dead volume within the tubing 102between the pump 162 and the handpiece 104. The proximity of the pump162 to the handpiece 104 can also improve the precision and control ofdrug penetration, drug diffusion, volume injection, and flow rate.

The pump 162 can include an interface (e.g., user interface) which canreceive commands to control the pump 162, for example, to display astatus of the pump 162 and information about the status of the deliveryof the drug to the patient. The pump 162 can include a plurality ofinputs, which can be physical inputs (e.g., buttons, sliders), virtualinputs (e.g., inputs provided via a display or touchscreen). Theinterface can receive commands to control the pump from one or moreinputs. For example, via the inputs, a user can navigate the interfaceof the pump 162 to, for example, determine the status of the pump 162and select injection parameters. The status of the pump 162 can includean amount of remaining drugs in the reservoirs or an amount of drugsdelivered via the pump 162, current power level of the power supply. Theinjection parameters can include fluid injection rate, total allowedfluid injection volume, selection of which fluid to inject, the sequenceor order of fluid injection, and withdrawal rate. The pump 162 caninclude pump reservoirs to deliver drugs from one or more reservoirs tothe handpiece 104 via the tubing 102. Each reservoir can store adifferent type of drug than other reservoirs. The reservoirs can besituated within the pump 162. The reservoirs can be external to the pump162. The pump 162 can include a strap to mount the pump 162 onto asurface (e.g. floor, ceiling, pole, etc.). The pump 162 can be equippedto a portion of a user (e.g. wrist, torso, arm, or other part of a body)to enable ergonomic use of the system and to leave the user's hands freeto perform other tasks during the injection of the fluid.

The pump 162 can include a processor to control the function of the pump162. The processor can be any type of single or multi-core processor orspecial purpose logic circuitry such as an FPGA (field programmable gatearray) or an ASIC (application specific integrated circuit). In someimplementations, the processor can include one or more antennas toenable the processor (and pump 162) to communicate with externaldevices. For example, the processor can communicate with an externalcontroller or remote that can be used to start, stop, or pause the flowof fluid to the handpiece 104. The external controller or remote can beoperated by a second user other than the user operating the pump 162.The pump 162 can include a power supply that can include batteries, suchas rechargeable batteries, or a capacitor that can supply power to thecomponents of the pump 162. The power supply can include an alternatingcurrent (AC) to direct current (DC) converter. For example, the pump 162can be plugged into an AC mains. The power supply can convert the powerfrom the AC mains into DC power that can be used by the processor andother components of the pump 162.

The pump 162 can include a plurality of pumps 162. For example, the pump162 can include a different pump 162 for each of the reservoirs. Each ofthe different pumps 162 can be the same type of pump or a different typeof pump. The pump 162 can include one or more of a lead screw-drivenmini syringe pump, 3-actuator pump, mini peristaltic pump, orpneumatic/hydraulic-driven pump. The pneumatic/hydraulic-driven pump canbe driven by an external pressure source that can be coupled with thepump 162 to drive the pump 162. In some implementations, differentconfigurations of the pump 162 with different pumps types can beselected based on the drug or fluid within the reservoirs. For example,a first pump type can be used for fluids with a relatively highviscosity and a second pump type can be used for fluids with arelatively low viscosity. In some implementations, one or more pumps 162can withdraw a fluid from the cavity. These pumps 162 can be referred toas vacuum pumps. The pumps 162 can withdraw the fluid into a separatereservoir configured to store the withdrawn fluid. In someimplementations, the vacuum pump can be an independent pump that isconfigured to only withdraw fluid from the cavity. In someimplementations, the pumps 162 can be configured to operate in multipledirections such that during a first time period or phase the pumps 162can pump fluid into the cavity, and during a second time period or phasethe pumps 162 can withdraw fluid from the cavity. In someimplementations, a first pump acting as a vacuum pump can operate at thesame time as a second pump flows fluid into a cavity such that theamount of fluid removed by first pump is substantially the same as theamount of fluid injected by the second pump.

The handpiece 104 can be used to deliver a drug to the patient (e.g.,based on the drug being driven by the pump 162). The drug can begenerally referred to as a fluid. The drug can be a gel. The fluid canbe a two-part gel. For example, a first part of the gel can be stored ina first reservoir, and a second part of the gel can be stored in asecond reservoir. The system 100 can mix the two parts of the gel justprior to injection via the handpiece 104. The fluid can include largemolecules such as proteins, antibodies, genes, DNA, RNA, particles,viruses, liposomes, nanoparticles, microspheres, and magnetic drugdelivery particles. Each fluid in the different reservoirs can be thesame or different fluids. In some implementations, one or morereservoirs can be initially empty, and the pump 162 can be used to drawfluid from the patient which can be stored in the reservoirs.

FIG. 3 illustrates a side view of an example handpiece 104 fordelivering fluid to a patient's cavity such as the inner ear. The fluidcan be any therapeutic substance or therapeutic agent. The handpiece 104includes a tool shaft 106, an angled portion 108, and a tip portion 110.The tip portion 110 can also include a collar 112. The tip portion 110can be used to pierce membranes or other thin tissue. For example, thehandpiece 104 can be inserted into the ear canal of the patient for thetranscanal delivery of fluid to the cochlea via the round window. Thetip portion 110 can be used to pierce the round window membrane toenable fluid to be delivered to the cochlea. In some implementations,the handpiece 104 can at least a portion of transparent material throughwhich flow of drug or components of the drug are viewable to a user. Thetransparent material can refer to a see through material, such as glass,acrylic, or plastic.

The handpiece 104 includes the tool shaft 106, the angled portion 108,and the tip portion 110. A surgeon can use the tool shaft 106 to holdand manipulate the handpiece 104 and position of the tip portion 110.The outer surface of the tool shaft 106 can include knurling to enable abetter grip of the handpiece 104 by the surgeon. The tool shaft 106includes a proximal end 200 and a distal end 202. The tool shaft 106 canhave a diameter of about 4 mm, 5 mm, or about 6 mm. The tool shaft 106can have a length of between about 90 mm and about 162 mm, between about90 mm and about 130 mm, or between about 100 mm and about 120 mm. Insome implementations, the length of the tool shaft 106 is 110 mm.

The distal end of the tool shaft 106 is coupled with the proximal end204 of the angled portion 108. The tip portion 110 is coupled with thedistal end 206 of the angled portion 108. The angled portion 108 isangled to enable the tip portion 110 to traverse the ear canal in aminimally invasive procedure and reach the round window. The angledportion 108 forms an angle 208 between the tool shaft 106 and the tipportion 110. The angle 208 can be about 170° and about 90°, betweenabout 170° and about 110°, between about 170° and about 120°, betweenabout 170° and about 140°, or between about 165° and about 155°. Theangle 208 can be defined as the angle between a longitudinal axis of thetool shaft 106 and a longitudinal axis of the tip portion 110. The angle208 is configured to enable transcanal positing of the tip portion 110at a patient's round window. The angle 208 can be selected to enable asurgeon to position the tip portion 110 at the round window and providethe surgeon visual access to the ear canal.

The tip portion 110 can be coupled with the distal end 206 of the angledportion 108. The distal portion of the tip portion 110 can be angled.The angle 210 can be between about 70° and about 140°, between about 75°and about 130°, between about 90° and about 120°, between about 100° andabout 120°, or between about 110° and about 120°. For example, the angle210 can be about 105°, 106°, 107°, 108°, 109°, 110°, 111°, 112°, 113°,114°, 115°, 116°, 117°, 118°, 119°, or 120°. The angle 210 can beselected to position the distal portion of the tip portion 110substantially perpendicular to the round window when the handpiece 104is inserted through the ear canal. The angle 210 can be selected basedon the anatomical configuration of the patient's inner and middle ear.For example, the surgeon can select a handpiece 104 with an appropriateangle 210 based on the position and angle of the round window and theround window niche. In some implementations, the surgeon can determinewhich angle 210 to select using CT or MRI images of the middle and innerear. The handpiece 104 can be manufactured with different angle 210configurations. In some implementations, the surgeon can bend the tipportion 110 to alter the angle 210 during a procedure.

The tip portion 110 can include a collar 112. The collar 112 can beconfigured to seat with a cavity of a patient including a round windowof a patient's cochlea, for example. The collar 112 can seal the roundwindow once the tip portion 110 pierces the round window membrane. Thecollar 112 can also control the depth the end of the tip portion 110 canbe inserted into the cochlea. The collar 112 can include a medical-gradesilicone. The collar 112 can be substantially domed or semi-spherical inshape. The diameter of the collar 112, at the collar's widest, can bebetween about 0.5 mm and about 3 mm, between about 0.5 mm and about 2.5mm, between about 1 mm and about 2 mm, or between about 1.5 mm and about2 mm.

The handpiece 104 can have an overall length 212 between about 130 mmand about 170 mm, between about 140 mm and about mm, or between about140 mm and about 162 mm. While described as different portions, the toolshaft 106, the angled portion 108, and the tip portion 110 can each bemanufactured as single or multiple pieces. For example, the handpiece104 can include one, two, or three separate pieces. The handpiece 104can be separable at the interface between any of the tool shaft 106, theangled portion 108, and the tip portion 110. In some implementations,the interface between the tool shaft 106, the angled portion 108, andthe tip portion 110 does not indicate that the portions are separable.For example, the tool shaft 106, the angled portion 108, and the tipportion 110 can be manufactured as a single piece. In otherimplementations, the angled portion 108 and the tool shaft 106 can forma first piece, and the tip portion 110 can form a second piece. In someimplementations, the handpiece 104 is reusable. In otherimplementations, the handpiece 104 is disposable. The handpiece 104 canbe manufactured from medically-approved sterilizable materials. Forexample, the handpiece 104 can be manufactured from 316 stainless steelor a sterilizable plastic.

FIG. 4 illustrates a cross-sectional view of the example handpiece 104.The handpiece 104 can include a microfluidic channel 300. The handpiece104 can include a first and a second inlet 302 to receive two or morecomponents of a drug. The handpiece 104 can include an outlet 304 tooutput a mixed drug to within a cavity of a patient. The handpiece 104can include a mixing chamber 306. The mixing chamber 306 can include oneor more mixing elements 308. In some implementations, the first and thesecond inlet 302 and the outlet 304 can refer to portions of themicrofluidic channel 300.

The handpiece 104 can include an inlet 302 for each of the reservoirs.For example, each inlet 302 can be coupled with an independent reservoirvia a different tubing 102 (or an input of a multi-input tubing 102) ora different internal lumen of the tubing 102. The inlets 302 can delivertheir respective fluids (or components) from an independent reservoir tothe mixing chamber 306. The fluids can refer to different drugs. Thefluids from the independent reservoirs can mix within the mixing chamber306. For example, the fluids within the independent reservoirs can beactivated when the fluids are mixed together. In some implementations,it can be advantageous to mix and activate the fluids just prior todelivery of the fluids to the patient.

The handpiece 104 can include a mixing chamber 306. The different fluids(e.g., a first and second part of a two-part or multipart gel) from theindependent inlets 302 can mix within the mixing chamber 306 beforeentering the microfluidic channel 300. The mixing chamber 306 caninclude mixing elements 308 to mix the fluids that enter the mixingchamber 306. The mixing elements 308 can include helical mixers that mixthe fluids as the fluids are pushed (or flow) along the length of themixing chamber 306. The mixing elements 308 can include ribs,protrusions, fins, or other elements that can create non-laminar flowwithin the mixing chamber 306 to mix the fluids within the mixingchamber 306.

The microfluidic channel 300 can have a gauge of about 22. Themicrofluidic channel's gauge can be between about 12 and 28, betweenabout 16 and about 24, between about 18 and about 22, or between about20 and 22. The microfluidic channel 300 can have a dead volume ofbetween about 10 μL and about 25 μL, between about 15 μL and about 25μL, or between about 20 μL and about 25 μL.

The microfluidic channel 300 can include different portions. Forexample, each of the tool shaft 106, angled portion 108, and the tipportion 110 can include a different portion of the microfluidic channel300. The different portions can be a single channel or continuouschannel. In some implementations, the microfluidic channel 300 isseparable at the interface between one or more of the portions. In someimplementations, the microfluidic channel portions are separable nearthe interface between the different portions of the handpiece 104. Forexample, the microfluidic channel portion within the tip portion 110 canextend past the tip portion 110 (as illustrated in FIG. 5), and themicrofluidic channel portion within the angled portion 108 can stopprior to the distal end 206 such that a portion of the microfluidicchannel extending from the tip portion 110 can be received by the angledportion 108. In some implementations, the handpiece 104 can include aplurality of microfluidic channels 300. For example, the handpiece 104may not include a mixing chamber 306 and the different microfluidicchannels 300 can each be coupled with a different one of the inlets 302.In some implementations, a second microfluidic channel 300 can be usedto evacuate fluid from the cavity.

FIG. 5 illustrates a side view of the example handpiece 104. In someimplementations, one or more of the portions of the handpiece 104 areseparable from one another. FIG. 5 illustrates an example handpiece 104with a separable tip portion 110. The tip portion 110 can be separatedfrom the tool shaft 106 and the angled portion 108 to facilitatesterilization of the handpiece 104. The tip portion 110 can be separablefrom the angled portion 108 to enable the tip portion 110 to berecoupled with the angled portion 108 at a different rotational angle.The tip portion 110 can be rotated with respect to the angled portion108 without separating the tip portion 110 from the angled portion 108.The tip portion 110 can be rotated with respect to the angled portion108 to provide the surgeon with improved access to the round window. Forexample, the surgeon can adapt the default position of the tip portion110 to account for variability between patient anatomies. The handpiece104 can include gaskets or o-rings at the interface between theseparable portions. The separable portions can be coupled together withsnap-on connectors, friction-fit or press-fit connections, or Luer lockconnections.

FIG. 6 illustrates an example tip portion 110 for the example handpiece104. The tip portion 110 illustrated in FIG. 6 is separated from theangled portion 108 and the tool shaft 106 of the handpiece 104. The tipportion 110 can include a tip 500. The tip 500 can be a portion of themicrofluidic channel 300 extending from the body of the tip portion 110.In some implementations, all of the tip portion 110 can be rotated withrespect to the angled portion 108. In other implementations, the tip 500can be rotated within the tip portion 110. In either example, the tip500 can be rotated from the position illustrated in FIG. 5 to a secondposition 502, illustrated by the dashed lines.

FIG. 7 illustrates an example handpiece 104 with a compression fitting600. The compression fitting 600 can be a knurled nut. The compressionfitting 600 can couple the angled portion 108 with the tip portion 110.The compression fitting 600 can be loosened to enable the tip portion110 to rotate with respect to the angled portion 108. Once the surgeonselects a degree of rotation, the surgeon can tighten the compressionfitting 600 to lock the degree of rotation between the angled portion108 and the tip portion 110 in place. In other implementations, the tipportion 110 and the angled portion 108 can be held together with afriction-fit that enables the tip portion 110 to be rotated with respectto the tip portion 110.

FIG. 8 illustrates an enlarged view of the tip 500 of the examplehandpiece 104. The tip 500 can include a needle end 700. The needle end700 includes the outlet 304. The needle end 700 can be a blunt end orcan be beveled to form a point. The needle end 700 can be configured topierce the round window membrane. The needle end 700 extends past thecollar 112 by a length between about 1 mm and about 4 mm, between about2 mm and about 3 mm, or between about 2.5 mm and about 3 mm. Forexample, the needle end 700 can have a length of 2.7 mm. The needle end700 can have a gauge size between about 25 and about 30, between about26 and about 30, or between about 27 and about 30.

Once the collar 112 is seated into the round window, only the needle end700 projects into the cochlea. The collar 112 can control the depth theneedle end 700 projects into the cochlea. The needle end 700 can preventthe needle end 700 from projecting too far into the cochlea and damagingthe cochlea. The collar 112 can properly position the outlet 304 withinthe cochlea so that the therapeutic substance properly disperses throughthe cochlea. For example, if the outlet 304 is positioned too shallowinto the cochlea, the therapeutic substance can concentrate near theround window and not disperse through the cochlea. If the outlet 304 ispositioned too deep into the cochlea, the needle end 700 can causedamage or trauma to the cochlea. In some implementations, the tip 500 ismanufactured from a malleable material such that a surgeon can bend thetip 500 to alter the angle 210. The collar 112 can be coupled with thetip 500 with an adhesive. In some implementations, the tip 500 caninclude a groove in which the collar 112 is seated.

FIGS. 9A and 9B illustrate the tip 500 inserted into the round window.FIG. 9A illustrates the handpiece 104 inserted through the ear canalwith the tip 500 inserted into the round window 118. FIG. 9B illustratesan enlarged view, from FIG. 9A, of the tip 500 inserted into the roundwindow 118. The tip 500 can be used to pierce the round window membrane.The tip 500 can be inserted into the round window 118. The collar 112can be seated into the round window 118 and seal the round window 118 asfluid is injected into the cochlea 116. The collar 112 is tapered from adiameter smaller than the diameter of the round window 118 to a diameterthat is wider than the diameter of the round window 118. When the collar112 is depressed against the round window 118, the collar 112 canocclude the round window 118. The collar 112 can also be used to controlthe insertion depth of the tip 500 into the cochlea 116. For example,the collar 112 can prevent the tip 500 from being inserted into thecochlea past the collar 112. The portion of the collar 112 with adiameter wider than the diameter of the round window 118 cansubstantially stop the tip 500 from farther insertion of the tip 500into the cochlea 116. Moving the collar 112 towards the outlet 120 ofthe tip 500 reduces the depth to which the tip 500 can be inserted. Thecollar 122 can prevent the tip 500 from being inserted too far into thecochlea 116.

FIG. 10 illustrates a block diagram of an example method 1000 to flow afluid into the cochlea. The method 1000 can include establishing afluidic coupling between a pump and a handpiece tool connected via amulti-input tubing (ACT 1002). The method 1000 can include inserting atip of the shaft of an angled portion of the handpiece tool into acavity of a patient (ACT 1004). The method 1000 can include mixing aplurality of fluids received from the multi-input tubing by a mixingchamber of the handpiece tool (ACT 1006). The method 1000 can includeoutputting the mixed fluid via the microfluidic channel through theoutlet of the tip to within the cavity of the patient (ACT 1008).

As set forth above, the method 1000 can include establishing a fluidiccoupling between a pump and a handpiece tool connected via a multi-inputtubing (ACT 1002). Also referring to FIGS. 1-9, the system 100 caninclude a pump 162 that is coupled with a handpiece 104 to flow fluidthrough the handpiece 104 and out an outlet of the handpiece 104.

The pump 162 can include one or more reservoirs that each can include adifferent fluid. The fluid can be a therapeutic, drug, or other activeagent. The pump 162 can include one or more pumps that flow the fluidfrom the reservoirs to the handpiece 104 (or handpiece tool) via atubing 102. The handpiece 104 can include a microfluidic channel coupledto the multi-input tubing to receive components of a drug via one ormore reservoirs responsive to one or more pumps 162 of the pump 162.

The handpiece 104 can be any of the handpieces described herein. Forexample, the handpiece 104 can include a tool shaft that includes afirst distal end, a first proximal end, a first fluidic channel, and afirst longitudinal axis. The handpiece 104 can include an angled portionthat can include a second distal end, a second proximal end coupled withthe first distal end, a second fluidic channel in communication with thefirst fluidic channel, and a second longitudinal axis defining an obtuseangle with the first longitudinal axis. The handpiece 104 can include atip portion projecting from the angled portion and including an outletand a third fluidic channel in communication with the second fluidicchannel. The handpiece 104 can include a collar coupled with the tipportion. The handpiece 104 can include a mixing chamber 306 that can mixthe plurality of fluids received at the inlets 302 from the pump 162.The mixing chamber 306 can include mixing elements that can facilitatethe mixing of the fluids.

The method 1000 can include inserting a tip of the shaft of an angledportion of the handpiece 104 into a cavity of a patient (ACT 1004). Themethod 100 can insert the tip by piercing a round window membrane. Theround window membrane can be pierced with the tip portion of thehandpiece 104. For example, the provided handpiece 104 can be insertedthrough the ear canal. The handpiece angled portion 108 can beconfigured to enable transcanal access of the round window. The tip 500of the tip portion 110 can be angled to position the needle end 700substantially perpendicular to the round window and round windowmembrane. The needle end 700 can be pressed against the round windowmembrane to pierce the round window membrane. The collar 112 can couplewith the tip a predetermined distance from an outlet of the tip isconfigured to control a distance the tip projects into the cavity of thepatient. The collar 112 can prevent the needle end 700 from projectingtoo far into the cochlea and causing damage to the cochlea. The collar112 can seat into the round window to seal the round window as the fluidis injected into the cochlea. Based on the patient's anatomy, a surgeoncan set a rotational offset between the tip portion and the angledportion of the handpiece 104 to enable the needle end 700 to access theround window. Also based on the patient's anatomy, the surgeon can setthe angle 210 between the needle end 700 and the tip portion such thatthe outlet 304 is positioned substantially perpendicular to the roundwindow and round window membrane. CT or MRI scans of the patient'smiddle and inner ear can be conducted. The surgeon can measure theanatomical angles of the patient's inner and middle ear to select theangle 210 of the tip portion 110. Also, based on the CT or MRI scans,the surgeon can select the length of the needle end 700 such that whenthe collar 112 is seated into the round window the outlet 304 isproperly positioned within the cochlea. The proper position of theoutlet 304 can be a depth into the cochlea that does not cause damage tothe cochlea but enables distribution of the fluid through the cochlea.

The method 1000 can include mixing the fluids received from themulti-input tubing by a mixing chamber 306 of the handpiece 104 (ACT1006). The mixing chamber 306 can include mixing elements that canfacilitate the mixing of the fluids. The mixing elements can refer tocomponents of the mixing chamber 306 to expedite the process of mixingthe components of the drug, such as a propeller, heat generator, or acompressor. For example, the pump 162 can transfer a first component anda second component from reservoirs to a mixing chamber 306 of thehandpiece 104 via tubes 102 corresponding to each component. The mixingchamber 306 can receive the first component and the second component viainlets 302. The mixing chamber 306 can mix the first component and thesecond component into a third component (or a mixed drug), for example,to output a mixed drug to within the cavity of a patient. In someimplementations, the method 1000 can include activating the pump 162 orthe mixing chamber 306 to mix components of a drug while the tip portion110 is projected into the cavity of a patient.

The method 1000 can include outputting the mixed fluids via themicrofluidic channel through the outlet of the tip to within the cavityof the patient (ACT 1008). The pump 162 can pump the fluid (or drug)from a reservoir, through the microfluidic channel 300, and into thecochlea via outlet 304. The method 1000 can include drilling, orotherwise forming, a ventilation hole in the stapes footplate. Theventilation hole can enable the release of pressure from the cochlea asthe pump flows the fluid into the cochlea. In some implementations, themethod 1000 can include withdrawing a fluid from the cochlea as fluid ispumped into the cochlea to maintain a constant pressure within thecochlea.

As described above, a method similar to the method 1000 can be performedto inject a fluid into other cavities of a patient. In someimplementations, the system can be used to inject fluids into an ocularcavity. For example, the handpiece tip can be inserted into the inferiortemporal quadrant 3.5 mm posterior to the limbus and a drug from thesystem's reservoirs can be injected into the vitreous cavity. Afterretracting the tip of the handpiece 104, the transcleral perforation canbe closed with a 50-μm-thick cyanoacrylate bioadhesive-fixed polyimidepatch.

In some implementations, the system 100 can be used to inject fluidsinto a spinal cavity. The system 100 can be used to deliver drugs intothe epidural space via the interlaminar, caudal, or transforaminalapproach. During the interlaminar approach, the handpiece tip can beplaced into the back of the epidural space and the drug can be deliveredover a wider area. During the caudal approach, the sacral hiatus can beused to enable the handpiece tip to be placed into the very bottom ofthe epidural space. Once injected, the drug can spread over severalspinal segments and cover both sides of the spinal canal. During thetransforaminal approach, the handpiece tip can be placed alongside thenerve as it exits the spine and the fluid can be injected into the“nerve canal.” The fluid can then travel up the nerve canal and into theepidural space from the side. This method can enable for a moreconcentrated delivery of the fluid into one affected area.

In some implementations, the system 100 can be used to inject fluidsinto a rectal cavity. During rectal surgery, the handpiece tip can beinserted into the rectal cavity to reach the rectal mucosa. Uponinsertion of the handpiece tip into the mucosa, fluid can be deliveredand the handpiece can be retracted. Areas nearby pathological tissue canbe injected to limit spreading of the disease. Prior to the drugdelivery, contrast dye can be premixed with the drug to confirm that thearea medication is traveling into the desired area.

In some implementations, the system 100 can be used to inject fluid intothe nasal cavity. For example, the drug can be injected into thebilateral maxillary sinus by inserting the handpiece tip into thesuperior meatus location of the olfactory epithelium. After reaching thearea near the olfactory epithelium, a gel can be injected via thehandpiece 104 that will release the gel's drug directly into the brain.

In some implementations, the system 100 can be used to inject fluidsinto the vaginal cavity. During cervical surgery, the handpiece tip canbe inserted into the cervix cavity. Areas nearby cancerous tissue can beinjected with the insertion of the handpiece tip to deliver fluidsadjacent to the cancerous tissue either before resection (to reducetumor size) or after resection (to reduce the risk of recurrence). Priorto the drug delivery, contrast dye can be used to confirm that themedication is traveling into the desired area.

While operations are depicted in the drawings in a particular order,such operations are not required to be performed in the particular ordershown or in sequential order, and all illustrated operations are notrequired to be performed. Actions described herein can be performed in adifferent order.

The separation of various system components does not require separationin all implementations, and the described program components can beincluded in a single hardware or software product.

Having now described some illustrative implementations, it is apparentthat the foregoing is illustrative and not limiting, having beenpresented by way of example. In particular, although many of theexamples presented herein involve specific combinations of method actsor system elements, those acts and those elements may be combined inother ways to accomplish the same objectives. Acts, elements andfeatures discussed in connection with one implementation are notintended to be excluded from a similar role in other implementations orimplementations.

The phraseology and terminology used herein is for the purpose ofdescription and should not be regarded as limiting. The use of“including” “comprising” “having” “containing” “involving”“characterized by” “characterized in that” and variations thereofherein, is meant to encompass the items listed thereafter, equivalentsthereof, and additional items, as well as alternate implementationsconsisting of the items listed thereafter exclusively. In oneimplementation, the systems and methods described herein consist of one,each combination of more than one, or all of the described elements,acts, or components.

As used herein, the term “about” and “substantially” will be understoodby persons of ordinary skill in the art and will vary to some extentdepending upon the context in which it is used. If there are uses of theterm which are not clear to persons of ordinary skill in the art giventhe context in which it is used, “about” will mean up to plus or minus10% of the particular term.

Any references to implementations or elements or acts of the systems andmethods herein referred to in the singular may also embraceimplementations including a plurality of these elements, and anyreferences in plural to any implementation or element or act herein mayalso embrace implementations including only a single element. Referencesin the singular or plural form are not intended to limit the presentlydisclosed systems or methods, their components, acts, or elements tosingle or plural configurations. References to any act or element beingbased on any information, act or element may include implementationswhere the act or element is based at least in part on any information,act, or element.

Any implementation disclosed herein may be combined with any otherimplementation or embodiment, and references to “an implementation,”“some implementations,” “one implementation” or the like are notnecessarily mutually exclusive and are intended to indicate that aparticular feature, structure, or characteristic described in connectionwith the implementation may be included in at least one implementationor embodiment. Such terms as used herein are not necessarily allreferring to the same implementation. Any implementation may be combinedwith any other implementation, inclusively or exclusively, in any mannerconsistent with the aspects and implementations disclosed herein.

The indefinite articles “a” and “an,” as used herein in thespecification and in the claims, unless clearly indicated to thecontrary, should be understood to mean “at least one.”

References to “or” may be construed as inclusive so that any termsdescribed using “or” may indicate any of a single, more than one, andall of the described terms. For example, a reference to “at least one of‘A’ and ‘B’” can include only ‘A’, only ‘B’, as well as both ‘A’ and‘B’. Such references used in conjunction with “comprising” or other openterminology can include additional items.

Where technical features in the drawings, detailed description or anyclaim are followed by reference signs, the reference signs have beenincluded to increase the intelligibility of the drawings, detaileddescription, and claims. Accordingly, neither the reference signs northeir absence have any limiting effect on the scope of any claimelements.

The systems and methods described herein may be embodied in otherspecific forms without departing from the characteristics thereof. Theforegoing implementations are illustrative rather than limiting of thedescribed systems and methods. Scope of the systems and methodsdescribed herein is thus indicated by the appended claims, rather thanthe foregoing description, and changes that come within the meaning andrange of equivalency of the claims are embraced therein.

What is claimed:
 1. A handpiece tool, comprising: a shaft comprising a first portion of a microfluidic channel configured to connect with a multi-input tubing to receive a plurality of fluids; an angled portion coupled with the tool shaft and comprising a second portion of the microfluidic channel, wherein the angled portion is configured to position a tip portion within a cavity of a patient, wherein the tip portion projects from the angled portion and comprises an outlet and a third portion of the microfluidic channel; a collar coupled with the tip portion at a predetermined distance from the outlet, the collar configured to control a distance the tip portion projects into the cavity of the patient; and a mixing chamber configured to receive, via the multi-input tubing, the plurality of fluids, mix the plurality of fluids to provide a mixed fluid, and output the mixed fluid via at least the third portion of the microfluidic channel through the outlet into the cavity of the patient.
 2. The handpiece tool of claim 1, wherein the mixing chamber further comprises a mixing element configured to mix the plurality of fluids, the mixing element including at least one of a rib, a protrusion, or a fin.
 3. The handpiece tool of claim 1, wherein the plurality of fluids comprises a plurality of multipart gels.
 4. The handpiece tool of claim 1, wherein the plurality of fluids comprise a plurality of drugs.
 5. The handpiece tool of claim 1, wherein the multi-input tubing comprises a plurality of tubing.
 6. The handpiece tool of claim 1, wherein the multi-input tubing is fluidly coupled to one or more pumps, the one or more pumps configured to pump the plurality of components to the multi-input tubing.
 7. The handpiece tool of claim 1, wherein each input of the multi-input tubing is fluidly coupled to an independent reservoir of a pump.
 8. The handpiece tool of claim 1, wherein the handpiece tool comprises a portion of transparent material through which flow of the plurality of fluids or the mixed fluid is viewable.
 9. The handpiece tool of claim 1, wherein the collar is configured to seat with the cavity of the patient comprising a round window of a patient's cochlea.
 10. The handpiece tool of claim 1, wherein the handpiece tool is configured to mix the plurality of fluids and deliver the mixed fluid via the outlet while the tip portion is projected into the cavity of the patient.
 11. A method, comprising: establishing a fluidic coupling between a handpiece tool and a pump using a tubing, the handpiece tool comprising a microfluidic channel coupled to the tubing to receive a plurality of fluids responsive to operation of one or more pumps of the pump; inserting a tip of the shaft of an angled portion of the handpiece tool into a cavity of a patient, wherein a collar coupled with the tip a predetermined distance from an outlet of the tip is configured to control a distance the tip projects into the cavity of the patient; mixing, by a mixing chamber of the handpiece tool, the plurality of fluids received from the multi-input tubing to provide a mixed fluid; and outputting the mixed fluid via the microfluidic channel through the outlet of the tip to within the cavity of the patient.
 12. The method of claim 11, further comprising mixing the plurality of fluids using a mixing element including at least one of a rib, a protrusion, or a fin.
 13. The method of claim 11, wherein the plurality of fluids comprises multipart gels.
 14. The method of claim 11, wherein the plurality of fluids comprise a plurality of drugs.
 15. The method of claim 11, wherein the multi-input tubing comprises a plurality of tubing.
 16. The method of claim 11, wherein each input of the multi-input tubing is fluidly coupled to an independent reservoir of a pump.
 17. The method of claim 11, wherein the handpiece tool comprises a portion of transparent material through which flow of the plurality of fluids or the mixed fluid is viewable.
 18. The method of claim 11, wherein the collar is configured to seat with the cavity of the patient comprising a round window of a patient's cochlea.
 19. The method of claim 11, further comprising mixing the plurality of fluids and delivering the mixed fluid via the outlet while the tip portion is projected into the cavity of the patient.
 20. The method of claim 11, further comprising activating one of the pump or the mixing chamber to mix the plurality of fluids while the tip portion is projected into the cavity of the patient. 